Title Dijagnostika i liječenje trombotičke trombocitopenične purpure
Title (english) Diagnosis and treatment of thrombotic thrombocytopenic purpura
Author Ana-Maria Prtenjača
Mentor Dražen Pulanić (mentor)
Committee member Ana Boban (predsjednik povjerenstva)
Committee member Jasenka Markeljević (član povjerenstva)
Committee member Dražen Pulanić (član povjerenstva)
Granter University of Zagreb School of Medicine (Department of Internal Medicine) Zagreb
Defense date and country 2022-07-15, Croatia
Scientific / art field, discipline and subdiscipline BIOMEDICINE AND HEALTHCARE Clinical Medical Sciences Internal Medicine
Abstract Trombotična trombocitopenična purpura (TTP) je rijetka mikroangiopatija karakterizirana
trombocitopenijom, mikroangiopatskom hemolitičkom anemijom, vrućicom, oslabljenom
bubrežnom funkcijom te neurološkim poremećajima. Uzrok TTP-a je nedostatak enzima
ADAMTS13 koji cijepa von Willebrandov faktor. Snižena razina aktivnosti ADAMTS13
uzrokuje stvaranje mikrotromba što vodi u ishemiju i oštećenje organa. Nedostatak
ADAMTS13 je najčešće stečen u odraslih (stečeni imunosni TTP, iTTP) i nastaje kao rezultat
stvaranja anti-ADAMTS13 antitijela. Ova antitijela neutraliziraju proteolitičku aktivnost
ADAMTS13 ili ubrzavaju njegovo otklanjanje iz plazme. Nasljedni kongenitalni oblik TTP-a
(cTTP) se najčešće otkrije u mlađoj dobi ili tijekom trudnoće. Ovaj tip bolesti nastaje kao
posljedica mutacije koja se nasljeđuje autosomno recesivno te uzrokuje smanjeno stvaranje
ADAMTS13.
Akutna epizoda TTP-a obično ima nespecifičnu inicijalnu kliničku sliku. Bolesnik može
razviti glavobolju, konfuziju, slabost, povraćanje ili proljev, a laboratorijski trombocitopeniju
i mikroangiopatsku hemolitičku anemiju, s ishemijom mikrocirkulacije različitih organa.
Tipična pentada simptoma koja uključuje vrućicu, promijenjeni mentalni status, anemiju,
trombocitopeniju i zatajenje bubrega razvije se u manje od 10% slučajeva.
Brzo postavljanje dijagnoze je važno jer je ovo hitno stanje sa visokom smrtnošću bez
liječenja. U bolesnika sa visokom kliničkom sumnjom na TTP preporuča se uzeti uzorak
plazme za testiranje aktivnosti ADAMTS13 i anti-ADAMTS13 IgG antitijela prije
započinjanja terapije.
U prvoj akutnoj epizodi te u relapsima iTTP-a preporuča se primijeniti terapijsku izmjenu
plazme (TPE) uz kortikosterode te razmotriti primjenu rituksimaba i kaplacizumaba. U
asimptomatskih slučajeva iTTP-a s niskom plazmatskom aktivnošću ADAMTS13 može se
koristiti rituksimab, dok se u trudnoći preporuča profilaktička upotreba TPE. Za
asimptomatske slučajeve cTTP-a preporuča se profilaktički upotrijebiti infuziju plazme u
trudnica. Za asimptomatske slučajeve cTTP-a izvan trudnoće preporuča se periodična
primjena infuzije plazme ili oprezna opservacija. Ispituju se i novi lijekovi, poput
rekombinantnog ADAMTS13.
U zaključku, TTP je rijetka ali životno ugrožavajuća bolest na koju se treba uvijek posumnjati
kod mikroangiopatske hemolitičke anemije s trombocitopenijom. Bolest ima šaroliku kliničku
sliku s ishemijom i trombozama različitih organa, potrebna je žurna dijagnostička obrada i
hitno liječenje kako bi se spriječila inače visoka smrtnost.
Abstract (english) Thrombotic thrombocytopenic purpura (TTP) is a rare microangiopathy characterised by
thrombocytopenia, microangiopathic haemolytic anaemia, fever, impaired renal function and
neurological disorders. The cause of TTP is deficiency of an enzyme that cleaves von
Willebrand's factor called ADAMTS13. Lower serum level of ADAMTS13 activity leads to
the formation of microthrombi causing ischaemia and organ damage. ADAMTS13 deficiency
is mostly immune-mediated in adults as a result of anti-ADAMTS13 antibody formation
(immune-mediated TTP, iTTP). These antibodies either neutralise the proteolytic activity of
ADAMST13 or accelerate its removal from plasma. The hereditary congenital form of TTP
(cTTP) is mostly detected in younger age or during pregnancy. This type of TTP is a result of
mutation characterised by autosomal recessive inheritance and it causes decreased
ADAMTS13 excretion.
An acute episode of TTP is characterised by nonspecific initial clinical presentation. The
patient can suffer from headache, confusion, weakness, vomiting or diarrhoea, while the
laboratory results can show thrombocytopenia and microangiopathic haemolytic anaemia,
along with microcirculatory ischaemia of various organs. The typical pentad including fever,
altered mental status, anaemia, thrombocytopenia and kidney failure develops in less than
10% of cases.
Timely diagnosis is important because this condition is considered a medical emergency and
has a high mortality rate if untreated. In patients with a high clinical suspicion of TTP it is
recommended to collect a plasma sample for testing ADAMTS13 activity and anti-
ADAMTS13 IgG antibodies before initiating therapy.
For the first acute episode and relapses of iTTP, it is strongly recommended to add
corticosteroids to therapeutic plasma exchange (TPE) and to consider adding rituximab and
caplacizumab. In asymptomatic cases of iTTP with low plasma ADAMTS13 activity it is
recommended to use rituximab, whereas during pregnancy prophylactic TPE is advised . For
asymptomatic cases of cTTP it is suggested to use plasma infusion during pregnancy as a
prophylaxis. For asymptomatic cases of cTTP outside of pregnancy it is recommended to use
either plasma infusion periodically or a watch and wait approach. Some new drugs are
currently being tested, such as recombinant ADAMTS13.
In conclusion, TTP is a rare life-threatening disease which should always be suspected in
cases with microangiopathic haemolytic anaemia with thrombocytopenia. It has various
clinical presentations with ischaemia and thrombosis affecting various organs, timely
diagnosis and treatment are needed to prevent the otherwise high mortality rate.
Keywords
trombotična trombocitopenična purpura
ADAMTS13
terapijska izmjena plazme
rituksimab
kaplacizumab
Keywords (english)
thrombotic thrombocytopenic purpura
ADAMTS13
therapeutic plasma exchange
rituximab
caplacizumab
Language croatian
URN:NBN urn:nbn:hr:105:344619
Study programme Title: Medicine Study programme type: university Study level: integrated undergraduate and graduate Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resource Text
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Created on 2023-02-10 09:53:44